| Objective: To explore the pathogenesis of programmed death-1(PD-1),cytotoxic T lymphocyte-associated antigen-4(CTLA-4)and cytokines in low-risk myelodysplastic syndrome,we investigated the expression level of PD-1,CTLA-4 on different T-cell subsets and regulatory T cells(Treg),tumor necrosis factor alpha(TNF-a),interferon gamma(IFN–?),transforming growth factor beta(TGF-?)and interleukin-10(IL-10)in peripheral blood(P BL)from low-risk MDS before and after treatment,as well as normal controls.Then we analyzed the change and correlation of PD-1,CTLA-4 and above cytokines.Methods: We collected 19 cases of newly diagnosed low-risk MDS patients from department of hematology of the second hospital of lanzhou university during December 2015 to January 2017,all patients were treated with cyclosporine A(Cs A)combined thalidomide and 10 cases of normal controls were enrolled into the present study.The proportion of PD-1,CTLA-4 on different T-cell subsets and Treg in PBL were measured by flow cytometry,the concentration of TNF-a,IFN–?,TGF-? and IL-10 levels were detected using ELISA.Then we analyzed the correlation between PD-1,CTLA-4 and above cytokines.Results: 1 The proportion of PD-1 on CD3+T in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(11.2±2.28% vs 4.16±2.01%,P<0.01);The proportion of PD-1 on CD4+T in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(9.90±3.41% vs 2.29±1.09%,P<0.01);The proportion of PD-1 on CD8+T in P BL of low-risk MDS patients before treatment were higher comparing with normal controls(9.45±2.27% vs 3.93±0.81%,P<0.01);The proportion of PD-1 on Treg in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(14.80±2.02% vs 4.55±1.01%,P<0.01);The proportion of PD-1 on CD3+T in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(6.13±1.80% vs 11.2±2.28 %,P<0.01);The proportion of PD-1 on CD4+T in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(5.12±2.08% vs 9.90±3.41%,P<0.01);The proportion of PD-1 on CD8+T in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(4.04±0.91% vs 9.45±2.27%,P<0.01);The proportion of PD-1 on Treg in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(6.68±1.38% vs 14.80±2.02 %,P<0.01).The level of PD-1 on CD3+T in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment(4.16±2.01% vs 6.13±1.80%,P<0.05).The level of PD-1 on CD4+T in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment(2.29±1.09% vs 5.12±2.08%,P<0.01).The level of PD-1 on CD8+T in PBL of normal controls there was no significant difference than that in the low-risk MDS patients after treatment(3.93±0.81% vs 4.04±0.91%,P=0.75).The level of PD-1 on Treg in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment(4.55±1.01% vs 6.68±1.38 %,P<0.01).2 The proportion of CTLA-4 on CD3+T in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(5.35±4.19% vs 0.52±0.21%,P<0.01);The proportion of CTLA-4 on CD4+T in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(2.79±0.70% vs 0.52±0.26%,P<0.01);The proportion of CTLA-4 on CD8+T in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(4.8±0.90% vs 1.44±0.62%,P<0.01);The proportion of CTLA-4 on Treg in PBL of low-risk MDS patients before treatment were higher comparing with normal controls(10.87±2.17% vs 2.39±0.61%,P<0.01);The proportion of CTLA-4 on CD3+T in PBL of low-risk MDS patients after treatment were lower than that in patient before treatment(1.41±1.06% vs 5.35±4.19%,P<0.01);The proportion of CTLA-4 onCD4+T in PBL of low-risk MDS patients after treatment were lower than that in patient before treatment(1.53±0.42% vs 2.79±0.70%,P<0.01);The proportion of CTLA-4 on CD8+T in PBL of low-risk MDS patients after treatment were lower than that in patient before treatment(2.25±0.64% vs 4.80±0.90%,P<0.01);The proportion of CTLA-4 on Treg in PBL of low-risk MDS patients after treatment were lower than that in patient before treatment(5.81±1.60% vs 10.87±2.17%,P<0.01);The level of CTLA-4 on CD3+T in PBL of normal controls were decreased than that in low-risk MDS patients after treatment(0.52±0.21% vs 1.41±1.06%,P<0.05).The level of CTLA-4 on CD4+T in PBL of normal controls were decreased than that in low-risk MDS patients after treatment(0.52±0.21% vs 1.41±1.06%,P<0.05).The level of CTLA-4 on CD8+T in PBL of normal controls were decreased than that in low-risk MDS patients after treatment(1.44±0.62% vs 2.25±0.64%,P<0.01).The level of CTLA-4 on Treg in PBL of normal controls were decreased than that in low-risk MDS patients after treatment(2.39±0.61% vs 5.81±1.60 %,P<0.01).3 The level of TNF-a in PBL of low-risk MDS patients before treatment increased signif icantly comparing with normal controls(30.57±7.65 vs 6.18±1.49,P<0.01);The level of IFN-? in PBL of low-risk MDS patients before treatment increased signif icantly comparing with normal controls(11.13±1.41 vs 5.35±1.26,P<0.01);The level of IL-10 in P BL of low-risk MDS patients before treatment increased signif icantly comparing with normal controls(43.62±5.83 vs 4.90±1.31,P<0.01);The level of TGF-? in PBL of low-risk MDS patients before treatment increased signif icantly comparing with normal controls(21.47±2.65 vs 16.30±2.52,P<0.01).The level of TNF-a in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(17.63±2.79 vs 30.57±7.65,P<0.01);The level of IFN-? in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(7.68±1.48 vs 11.13±1.41,P<0.01);The level of IL-10 in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(13.34±3.89 vs 43.62±5.83,P<0.01);The level of TGF-? in PBL of low-risk MDS patients after treatment were lower than that in patients before treatment(17.09±1.26 vs 21.47±2.65,P<0.01).The level of TNF-a in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment(6.18±1.49 vs 17.63±2.79,P<0.01).The level of IFN-? in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment(5.35±1.26 vs 7.68±1.48,P<0.01).The level of IL-10 in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment(4.90±1.31 vs 13.34±3.89,P<0.01).The level of TGF-? in PBL of normal controls were decreased than that in the low-risk MDS patients after treatment there was no significant difference(16.30±2.52 vs 17.09±1.26,P=0.26).4 The proportion of PD-1 on CD4+T in low-risk MDS patients before treatment was positively correlated with the level of TNF-a,IFN-?;The proportion of PD-1 on Treg in low-risk MDS patients before treatment was positively correlated with the level of IL-10,TNF-a,and IFN-?.The proportion of CTLA-4 on CD4+T in low-risk MDS patients before treatment was positively correlated with the level of IL-10;The proportion of CTLA-4 on Treg in low-risk MDS patients before treatment was positively correlated with the level of IL-10 and TGF-?.Conclusion: 1 The proportion of PD-1 on different T-cell subsets and Treg increased in low-risk MDS patients,indicating that PD-1,CTLA-4 participate in MDS immune disorder by regualting the function of T-cell subsets and Treg;2 The level of TNF-a,IFN-?,IL-10 and TGF-? increased in low-risk MDS patients and correlated with the expression of PD-1,CTLA-4,indicating PD-1,CTLA-4 on T-cell subsets and Treg along with TNF-a,IFN-?,IL-10 and TGF-? participate in MDS immune disorder. |
PDF Full Text Request